Impaired growth in the first trimester of gestation was associated with an adverse cardiovascular risk profile at age 6, researchers found.

Action Points

Fetal crown-to-rump length can be used as a first trimester growth outcome.

This study found that impaired first trimester fetal growth, as measured by fetal crown-to-rump length, was associated with an adverse cardiovascular risk profile in school-age children.

Impaired growth in the first trimester of gestation was associated with an adverse cardiovascular risk profile at age 6, researchers found.

Children whose fetal crown-to-rump lengths were shortest in the first trimester had higher total fat mass at age 6, as well as higher android/gynoid fat mass ratios and high diastolic blood pressure and total cholesterol, compared with children with the longest crown-to-rump lengths (all P<0.05), researcher Vincent Jaddoe, MD, PhD, of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues reported.

The study showed for the first time that first trimester fetal crown-to-rump length is associated with an adverse cardiovascular risk profile in childhood, the researchers wrote in BMJ, published online Jan. 24.

Fetal Growth Impact Not Known

Fetal development is greatest during the first trimester of pregnancy. Although there is much speculation that first trimester growth may influence cardiovascular health in adulthood, the link between impaired early fetal growth and heart and vascular disease risk in adulthood remains unproven, the researchers noted.

"Whether first trimester fetal growth restriction is associated with risk factors for cardiovascular disease in later life remains unknown," they wrote.

In an effort to determine if an association existed, Jaddoe and colleagues conducted a nested prospective cohort study that included 1,184 children followed from just after conception to age 6. All children included in the study had first trimester fetal crown-to-rump length measurements and all had mothers with a known first day of her last menstrual period and a regular cycle. Second and third trimester fetal head circumference, abdominal circumference, and femur length were also measured to the nearest millimeter using standard ultrasound procedures.

At age 6 (range 5.7 to 6.8), the children's body mass indexes (BMI) were assessed, along with their total and abdominal fat distribution, blood pressure and blood concentrations of cholesterol, triglycerides, insulin, and C peptide.

Clustering of cardiovascular risk factors was defined as having three or more of the following: high android fat mass; high systolic or diastolic blood pressure; low high density lipoprotein cholesterol or high triglycerides concentrations; and high insulin concentrations.

Information on possible confounding maternal risk factors was obtained from the mothers through questionnaires filled out at enrollment, and the mothers' BMI and blood pressure were also measured during this time.

The researchers used first trimester fetal crown-to-rump length standard deviation scores as a continuous variable to analyze the linear association of crown-to-rump length with childhood outcomes. They categorized first trimester fetal crown-to-rump length by fifths and used various multivariate regression models and linear regression models to examine the association between crown-to-rump length and outcomes at age 6.

Longitudinal growth analyses showed that compared with school-age children without clustering of cardiovascular risk factors, those with clustering had a smaller first trimester fetal crown-to-rump length and lower second and third trimester estimated fetal weight growth, but higher weight growth from the age of 6 months.

One study limitation cited by the researchers was the fact that only a small percentage of the original population-based study cohort could be included in the analysis. This group tended to be healthier and better educated, which might affect the generalizability of the findings, the researchers wrote.

They concluded that the findings add to the growing evidence that the first trimester of pregnancy may be a critical time for the development of cardiovascular risk factors later in life.

Study 'Hypothesis Generating'

In an editorial published with the study, Gordon C.S. Smith, MD, PhD, of the University of Cambridge in England, wrote that the study must be viewed as "hypothesis generating," noting that the authors themselves acknowledged that some of their findings may have happened by chance.

But he added that "the pre-existing body of work suggests that Jaddoe and colleagues' findings will be reproducible."

He noted that for doctors, the most pertinent question is whether these early effects can be modified with interventions to promote more normal growth trajectories.

"Given the potential for interventions to cause serious harm at this stage of pregnancy, compelling evidence of safety will be needed before their evaluation," he wrote. "Hence, the appropriate response in the short term is that we need a deeper understanding of the strength, nature, and mechanisms of the reported associations before rushing in to intervene."

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